This invention relates to organic compounds and compositions which have useful therapeutic properties. More particularly, the invention concerns novel pregnene compounds having anti-proliferative and antitumor activities, pharmaceutical compositions comprising such compounds, and methods of their use for therapeutic purposes.
Of great importance to man is the control of pathological cellular proliferation such as that which occurs in the case of cancer. Considerable research and resources have been devoted to oncology and antitumor measures including chemotherapy. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting, or controlling the growth of, for example, tumors, new methods and antitumor chemical compositions are needed. Anti-proliferative agents can also be useful in treating autoimmune diseases and inflammatory disease.
In searching for new biologically active compounds, it has been found that some natural products and organisms are potential sources for chemical molecules having useful biological activity of great diversity. For example, the diterpene commonly known as paclitaxel, isolated from several species of yew trees, is a mitotic spindle poison that stabilizes microtubules and inhibits their depolymerization to free tubulin (Fuchs, D. A., R. K. Johnson [1978] Cancer Treat. Rep. 62:1219-1222; Schiff, P. B., J. Fant, S. B. Horwitz [1979] Nature (London) 22:665-667). Paclitaxel is also known to have antitumor activity and has undergone a number of clinical trials which have shown it to be effective in the treatment of a wide range of cancers (Rowinski, E. K. R. C. Donehower [1995] N. Engl. J. Med. 332:1004-1014). See also, e.g., U.S. Pat. Nos. 5,157,049; 4,960,790; and 4,206,221.
Marine soft corals have also proven to be a source of biologically active chemical molecules. A number of publications disclose organic compounds derived from marine soft corals including Scheuer, P. J. (ed.) Marine Natural Products, Chemical and Biological Perspectives, Academic Press, New York, 1978-1983, Vol. I-V; Faulkner, D. J. (2002) Nat. Prod. Rep. 19:1-48; Faulkner, D. J. Nat Prod Rep. (2001)18:1-49; Faulkner, D. J. (2000); Nat. Prod. Rep 17:7-55; Long B H, Carboni J M, Wasserman A J, Cornell L A, Casazza A M, Jensen P R, Lindel T, Fenical W, Fairchild C R. (1998) xe2x80x9cEleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol).Cancer Res 58:1111-5.
Marine soft corals have been the source of a number of natural pregnene analogs. For example: Pregna-5,20-dien-3-ol has been isolated from the soft coral Gersemia rubiformis Kingston, J. F.; Gregory, B.; Fallis, A. G., J. Chem. Soc., Perkin Trans. I 1979, 1, 2064. Pregna-5,20-dien-3-ol-xcex2-D-Galactopyranoside has been isolated from the gorgonian coral of the genus Pseudoplexaura waagenaari (Wasylyk, J. M.; Martin, G. E.; Weinheimer, A. J.; Alam, M. J. Nat. Prod. 1989, 52, 391) 18-acetoxypregna-1,4,20-trien-3-one, has been reported from the soft coral Telesto riseii Ross, R. A.; Scheuer, P. J. Tetrahedron Lett. 1979, 4701; 11-acetoxypregna-4,20-dien-3-one from the gorgonian Eunicella cavolini (Cimino, G.; Desiderio, B.; De Stefano, S.; Sodano, G. Experientia 1978, 35, 298) and 3-O-(4-O-acetyl-alpha-L-fucopyranoside) from a gorgonian Eunicea sp. (Cobar, O. M. Rodriguez A. D., Padilla, O. L., J. Nat. Prod. 1997, 60, 1186-1188).
A principal object of the subject invention is the provision of novel compositions of biologically active compounds which have utility for use in promoting apoptosis and inhibiting cellular proliferation. In a specific embodiment, the compounds and compositions of the subject invention can be used in the treatment of cancer.
One aspect of the current invention concerns the novel compound Swiftiapregnene (I). Advantageously, Swiftiapregnene can inhibit unwanted cellular proliferation, including the proliferation of tumor cells. 
In a specific embodiment, the novel compositions and methods of the subject invention can be used in the treatment of an animal hosting cancer cells including, for example, inhibiting the growth of tumor cells in a mammalian host. More particularly, the subject compounds can be used for inhibiting in a human the growth of tumor cells, including cells of breast, colon, CNS, ovarian, renal, prostate, liver, pancreatic, uterine, or lung tumors, as well as human leukemia or melanoma cells. The mechanisms for achieving anticancer activity exhibited by the subject compounds would lead a person of ordinary skill in the art to recognize the applicability of the subject compounds, compositions, and methods to additional types of cancer as described herein.
In specific embodiments, the subject invention provides new glycosylated pregnenes, as exemplified by Swiftiapregnene (I). Swiftiapregnene has not been isolated previously from a natural source nor have they been previously synthesized.
In accordance with the subject invention, methods for inhibiting cancer cells in a host include contacting tumor cells with an effective amount of the new pharmaceutical compositions of the invention. The cancer cells inhibited by the invention are those which are susceptible to the subject compounds described herein or compositions comprising those compounds.
Additional aspects of the invention include the provision of methods for producing the new compounds and compositions.
Other objects and further scope of applicability of the present invention will become apparent from the detailed descriptions given herein; it should be understood, however, that the detailed descriptions, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent from such descriptions.